• Biotherapeutics

    Science Saturday: Pioneering living donor cartilage transplants

Mayo Clinic is poised to establish what is believed to be the first-ever living cartilage donor bank to provide a new regenerative option for healing common knee injuries. That donor bank will lay the foundation for living donor musculoskeletal tissue transplants — a first at Mayo Clinic and possibly in the world — to help restore knee function.

Mayo Clinic's Center for Regenerative Medicine supports this work in collaboration with Mayo Clinic Orthopedics and Sports Medicine as part of the center's strategic objective of advancing the practice.

Mario Hevesi, M.D., Ph.D.

"Some patients have damage in their knee cartilage that I compare to a single large pothole in an otherwise smooth road. So for these patients, we say the perfect thing is to resurface that pothole rather than pull out the entire road and put in a knee replacement," says Mario Hevesi, M.D., Ph.D., an orthopedic surgeon at Mayo Clinic. "A living cartilage transplant could biologically fix that pothole while preserving healthy cartilage and restoring functionality to the native knee."

Whether it is from an athletic injury, an accidental sprain, or everyday wear and tear, cartilage defects can progress to more generalized joint degeneration. Some people suffer from osteochondritis dissecans, a condition in which bone under the cartilage dies and causes cartilage to break loose. Whatever the cause, cartilage defects are painful and can severely limit mobility.

Cartilage — the smooth tissue at the end of bones that cushions the joints, allowing them to glide together smoothly — cannot regenerate itself. Therein lays a treatment dilemma for people under 50 who are often not ready for a total knee replacement.

Daniel Saris, M.D., Ph.D.

"If the defect is small, we can take the patient's own cartilage, culture in it the lab and use it to repair the knee. When the defect is large, the patient would need additional cartilage from a donor. It's like kidney disease. If your kidney fails, it does not heal itself. That's why surgeons perform kidney transplants. That same could be said when cartilage fails. A transplant is needed," says Daniel Saris, M.D., Ph.D., an orthopedic surgeon at Mayo Clinic.

Cartilage transplants are currently performed using deceased donors. With a donor bank, healthy, living cartilage will be collected from patients who are undergoing knee replacement and have consented to donate pieces of leftover healthy cartilage and bone that otherwise would be discarded after surgery. A living donor cartilage bank would provide a new source of healthy cartilage tissue, potentially increasing access to and lowering the cost of a cartilage transplant.

"You can take that tissue that still has miles on it, if you use the analogy of tread wear, and that can be implanted in another patient. Then suddenly you've unlocked a whole new area of potential. We would no longer have to wait for a limited supply of cartilage from someone who has unfortunately passed away. We have better control over scheduling surgeries and the overall logistics of implantation," says Dr. Hevesi.

Mayo has been building the scientific case for the living donor cartilage bank for many years. Aaron Krych, M.D., first conceptualized the project, and Dr. Hevesi expanded and validated the quality in his doctoral dissertation. Together with Dr. Saris, they are evaluating the procedure for patient care.

Aaron Krych, M.D.

"The use of living donor cartilage would be a disruptive patient-centered innovation," says Dr. Krych. "Compared to current standard of care surgery in which the timing of receiving an allograft is unpredictable, a living donor cartilage program would allow patients to schedule their surgeries ahead of time to help them plan their post-op recovery and accommodations needed in work and life. In addition, the quality of the cells from our pre-clinical work shows a higher viability, which will hopefully lead to improved outcomes."

Mayo's data show that a living donor cartilage transplant consists of 94% living cells, compared to 46% living cells when using deceased donor cartilage from a commercial bone bank. The more viable the graft, the longer it is expected to last, potentially delaying the need for future knee replacement surgery.

Cartilage does not have blood vessels or nerves. Therefore, unlike organ transplantation, cartilage transplantation does not have an immune response risk.

"That creates the possibility of transplanting in a safer way because the transplant will not be part of the blood supply. Therefore, there's less risk of rejection from blood types not matching," says Dr. Saris. "The cartilage will function like cartilage does, only in a different location. The bone that comes with the cartilage will be replaced by the patient's own bone and grow into the patient's knee. Patients will not need any special medication after transplantation," says Dr. Saris.

The Center for Regenerative Medicine will oversee the cartilage donor bank. It will be a new component of Mayo Clinic's bone bank, which operates under Food and Drug Administration regulatory requirements to provide bone grafts for patients.

Mayo will perform the first living cartilage transplants under institutional and independent third-party review. Clinicians will evaluate data from the first patients to determine safety and effectiveness, and whether living cartilage should be recommended as standard of care in future transplantation.

The first living cartilage transplants at Mayo Clinic may be performed by the end of 2021. If successful, Mayo could eventually expand the use of living cartilage transplants to repair injuries in other joints, including hips, ankles, shoulders and elbows.